We have developed Biomarkers of Aging measuring proliferative potential and cellular turnover that correlate to the physiologic age of donor mice and are sensitive to interventions that either lengthen or shorten lifespan. The goal of this project on Biomarkers of Aging research is to use our past findings and developed techniques, as well as new ones to: 1) extend our studies on in vitro proliferation and in vivo turnover of cells from numerous sites in the body in mice which reveal the physiologic age of the of the donor animal, 2) provide nondamaging methods to assess physiologic age and predict lifespan by biopsies or blood samples which will be applicable to the human in future studies, 3) in preparation for this, apply our techniques to two nonrodent species, rhesus monkeys and dogs, and 4) to approach the mechanism by which our two treatments (caloric restriction and high levels of endogenous growth hormone) reduce or increase, respectively, both lifespan and our biomarkers' readouts in parallel. In order to do this we will: 1) Conduct cross sectional studies in 3 unrelated species on age and diet linked changes, using a panel of proliferation-related biomarkers 2) Conduct longitudinal studies using nonlethal biomarkers to determine how well they predict lifespan in mice and monkeys 3) Determine if animal models with high GH and IGF-1 levels display premature changes in proliferative biomarkers and aging 4) Carry out studies on possible mechanism(s) relating loss of replicative potential in high GH level animal models and its preservation by caloric restriction.